摘要
目的研究P13K／Akt信号通路在大鼠糖尿病神经病理痛中的作用。方法Wistar大鼠，体质量180～220g，腹腔单次注射链脲菌素65mg／kg制作糖尿病神经病理痛模型。4周后用Vonfrey纤维测双后足机械痛闽，痛闲明显下降者为糖尿病神经病理性疼痛造模成功。将64只成模大鼠随机分为两组：糖尿病神经病理痛组（D组）和P13K抑制剂组（Ⅰ组），另取同窝大鼠32只作为对照组（C组）。Ⅰ组大鼠静脉注射0．5mg／kg的P13K抑制剂Wortmannin，1次／天。于实验开始后第4、6、8、10周末，各组分别随机取8只大鼠，采用Vonfrey纤维丝测机械缩足反应阈值（MWT），用肌电图仪测定神经传导速度（NCV），用免疫组化和Western blot法检测脊髓和背根神经节（DRG）磷酸化Akt（p-Akt）水平。结果与C组比较，D组和Ⅰ组均在第4周开始出现MWT降低，NCV减慢（P〈0．05）并持续至第10周；与D组比较，在用药后各时点Ⅰ组MwT和NCV升高（P〈0．05）。与C组比较，在脊髓和背根神经节中，D组和Ⅰ组均在第4周开始出现P～Akt升高（P〈0．05），而D组上述改变持续至第10周；Ⅰ组第6周时出现p-Akt下降并持续至第10周（P〈0．05）。结论P13K／Akt信号通路参与了糖尿病大鼠神经病理痛的形成和维持。
Objective To investigate the role of PI3K/Akt signal pathway in diabetes neuropathic pain induced by streptozoein. Methods Wistar rats weighing 180-220g ,Diabetes neuropathic pain was induced by intraperitoneal streptozocin 65mg/kg ,and 64 rats with diabetic neuropathic pain were randomly divided into two groups：group Ⅱdiabetic neuropathic pain and group Ⅲ Ⅱ ＋ PI3K inhibitor,while 32 age matched rats were used to be group Ⅰ control. Then rats were group housed with full access to food and water. At the begin of fifth week, rats in group Ⅲreceived Wortmannin,a selective PI3K inhibitor 0.5mg/kg intravenous from tail vein once a day,while the animals in groupⅠ and Ⅱ received vehicle only. At the end of the fourth,sixth,eighth and tenth week, Paw withdrawal mechanical threshold（MWT） were measured by a set of Von Frey filaments. The animals were anesthetized and nerve conduction velocity （NCV） of left sciatic nerve was measured. The animals were then killed and the lumbar segment of the spinal cord and dorsal root ganglion （DRG） were removed for determination of the level of p-Akt by immunohistochemistry and western blots. Results The MWT was significantly lower and NCV slower and the level of p-Akt in DRG and the spinal cord was significantly higher in group Ⅱ than in group Ⅰat each time point. The selective inhibitor of PI3K significantly attenuated the abovementioned diabetes induced changes in group M. Conclusion The signal transduction pathway of PI3K/Akt is involved in the development of diabetic neuropathic pain in rats.
出处
《重庆医学》
CAS
CSCD
北大核心
2009年第14期1757-1759,共3页
Chongqing medicine
基金
湖北省卫生厅基金资助项目(JX3C58)。
